219823-47-9

Basic information

• Product Name: R)-3-(p-toluenesulfonyl) oxytetrahydrofuran
• Synonyms: R)-3-(p-toluenesulfonyl) oxytetrahydrofuran;(R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate;(R)-Toluene-4-sulfonic acid tetrahydrofuran-3-yl ester;(3R)-Tetrahydrofuran-3-yl 4-methylbenzenesulfonate;toluene-4-sulfonic acid (R)-(tetrahydro-furan- 3-yl) ester;(R)-(-)-3-tetrahydrofuranyl tosylate;(R)-Tetrahydrofuran-3-yl 40-methylbenzenesulfonate
• CAS NO: 219823-47-9
• Molecular Formula: C₁₁H₁₄O₄S
• Molecular Weight: 242.29
• EINECS: 1592732-453-0
• Mol File: 219823-47-9.mol
• Article Data: 24

Chemical Properties

• Boiling Point: 384.8±35.0 °C(Predicted)
• Appearance: /
• Density: 1.30±0.1 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• Solubility: Chloroform, Methanol (Slightly)
• CAS DataBase Reference: R)-3-(p-toluenesulfonyl) oxytetrahydrofuran(CAS DataBase Reference)
• NIST Chemistry Reference: R)-3-(p-toluenesulfonyl) oxytetrahydrofuran(219823-47-9)
• EPA Substance Registry System: R)-3-(p-toluenesulfonyl) oxytetrahydrofuran(219823-47-9)

Safety Data

• Hazardous Substances Data: 219823-47-9(Hazardous Substances Data)

Usage

Uses

(3R)-Tetrahydrofuran-3-yl 4-Methylbenzenesulfonate is derived from (R)-(-)-3-Hydroxytetrahydrofuran (H957760), which is a versatile chemical reactant used in the synthesis of pharmaceutical agents.

Synthetic route

(R)-3-Hydroxytetrahydrofuran (86087-24-3) + p-toluenesulfonyl chloride (98-59-9) → (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9)

Conditions	Yield
With pyridine In dichloromethane at 0 - 20℃; for 18h; Inert atmosphere;	100%
With potassium iodide; silver(l) oxide In dichloromethane at 40℃;	89%
Stage #1: (R)-3-Hydroxytetrahydrofuran With trimethylamine hydrochloride; triethylamine In dichloromethane at 20℃; for 0.333333h; Stage #2: p-toluenesulfonyl chloride In dichloromethane at 20℃;	83%

4'-hydroxy-biphenyl-4-carboxylic acid (R)-1-methyl-heptyl ester (121687-76-1) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 4'-[(R)-(tetrahydro-furan-3-yl)oxy]-biphenyl-4-carboxylic acid (R)-1-methyl-heptyl ester (1610514-57-2)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 60℃; for 4h;	91.7%

4-ethoxycarbonylpyrazole (37622-90-5) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → C10H14N2O3 (1589005-67-3)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 80℃; for 14h;	91%

4-bromo-phenol (106-41-2) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (S)-3-(4-bromophenoxy)tetrahydrofuran (857854-82-1)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 10h;	90.1%
With potassium carbonate In N,N-dimethyl-formamide at 85℃; for 15h;

(2-chloro-5-iodophenyl)(4-hydroxyphenyl)methanone (1459754-40-5) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (S)-(2-chloro-5-iodophenyl)(4-((tetrahydrofuran-3-yl)oxy)phenyl)methanone (915095-87-3)

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile at 50 - 55℃;	87%

(2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(4-chloro-3-(4-hydroxybenzyl)phenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (1079083-63-8) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(4-chloro-3-(4-(((S)-tetrahydrofuran-3-yl)oxy)benzyl)phenyl)tetrahydro-2H-pyran-3,4,5-trityl triacetate

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃;	87%

(R)-tert-butyl (2-(5-(2-fluoro-3-hydroxyphenyl)-3-(2-fluoro-6-(trifluoromethyl)benzyl)-4-methyl-2,6-dioxo-2,3-dihydropyrimidine-1(6H)-yl)-1-phenylethyl)carbamate + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → tert-butyl ((R)-2-(5-(2-fluoro-3-(((S)-tetrahydrofuran-3-yl)oxy)phenyl)-3-(2-fluoro- 6-(trifluoromethyl)benzyl)-4-methyl-2,6-dioxo-2,3-dihydropyrimidine-1(6H)-yl)-1-phenylethyl)carbamate

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 70℃; for 12h;	87%

C28H30O11 (903566-68-7) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 1,1-anhydro-1-C-[5-(4-((S)-tetrahydrofuran-3-yloxy)-phenyl)-methyl-2-(hydroxymethyl)phenyl]-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 12h;	79%

4-(3-(3-fluoro-4-hydroxyphenyl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (S)-4-(3-(3-fluoro-4-((tetrahydrofuran-3-yl)oxy)phenyl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile

Conditions	Yield
With caesium carbonate In N,N-dimethyl acetamide at 60℃; for 2h; Inert atmosphere;	77.9%
With caesium carbonate In N,N-dimethyl acetamide; water at 60℃; for 2h;	77.9%

tert-butyl (2R,4R)-4-amino-2-methylpiperidine-1-carboxylate + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → C15H28N2O3

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 95℃; for 48h;	76%

5-(4-fluoro-2-hydroxyphenyl)-9-{2-methyl-2-[3-(trifluoromethyl)phenyl]propanoyl}-1,3,9-triazaspiro[5.5]undecan-2-one + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 5-(4-fluoro-2-{[(3S)-oxolan-3-yl]oxy}phenyl)-9-{2-methyl-2-[3-(trifluoromethyl)phenyl]propanoyl}-1,3,9-triazaspiro[5.5]undecan-2-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 5h;	74%

4-hydroxy-benzaldehyde (123-08-0) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (S)-4-((tetrahydrofuran-3-yl)oxy)benzaldehyde

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 100℃; for 14h;	70%

methyl 3-hydroxy-5-(5-methyl-1,3-thiazol-2-yl)benzoate + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → methyl 3-(5-methyl-1,3-thiazol-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzoate

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 90℃; for 36h;	67%

3-bromo-5-hydroxy-benzoic acid methyl ester (192810-12-1) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → methyl 3-bromo-5-[(3S)-tetrahydrofuran-3-yloxy]benzoate

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 80℃;	67%

6-(4-hydroxy-1,2-dihydrofuro[3,2-f]quinolin-9-yloxy)-N-methyl-1-naphthamide + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (S)-6-((4-((tetrahydrofuran-3-yl)oxy)-1,2-dihydrofuro[3,2-f] quinolin-9-yl)oxy)-Ν-methyl-1-naphthamide

Conditions	Yield
With caesium carbonate In N,N-dimethyl acetamide at 60℃; for 0.5h; Inert atmosphere;	67%

4-bromo-3-methoxyphenol (102127-34-4) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → C11H13BrO3

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 80℃; for 16h;	64%

GSK333081 + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 1-isopropyl-3-(β-D-glucopyranosyloxy)-4-[4-((S)-tetrahydrofuran-3-yloxy)benzyl]-5-methyl-1H-pyrazole

Conditions	Yield
With caesium carbonate In DMF (N,N-dimethyl-formamide) at 50℃; for 16h;	60%

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-hydroxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (864070-37-1) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → empagliflozin (864070-44-0)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 75℃; for 21h;	57%
With caesium carbonate In N,N-dimethyl-formamide at 75℃; for 18h;	49%
With caesium carbonate In N,N-dimethyl-formamide at 75℃; for 18h;	49%
With caesium carbonate at 25 - 40℃;
With caesium carbonate In N,N-dimethyl-formamide at 30 - 45℃; for 24h;	0.55 kg

4-bromo-2(1H)-pyridinone (36953-37-4) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 4-bromo-1-[(S)-tetrahydro-furan-3-yl]-1H-pyridin-2-one (1237534-49-4) + 4-bromo-2-[(S)-tetrahydro-furan-3-yloxy]-pyridine (1237534-50-7)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 80℃;	A 16% B 56%
With potassium carbonate In dimethyl sulfoxide at 80℃;

4-(3-(6-hydroxypyridin-3-yl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (S)-4-(4,4-dimethyl-5-oxo-3-(6-((tetrahydrofuran-3-yl)oxy)pyridin-3-yl)-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile

Conditions	Yield
With caesium carbonate In N,N-dimethyl acetamide at 60℃; for 2h; Inert atmosphere;	52.6%
With caesium carbonate In N,N-dimethyl acetamide at 60℃; for 2h;	52.6%

4-(4-(methoxymethyl)-2-((1s,4s)-4-methylcyclohexylamino)-6-(oxetan-3-yloxy)pyrimidin-5-yl)phenol + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 4-(methoxymethyl)-N-((1s,4s)-4-methylcyclohexyl)-6-(oxetan-3-yloxy)-5-(4-((S)-tetrahydrofuran-3-yloxy)phenyl)pyrimidin-2-amine

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 20℃;	52%

5-(4-fluoro-2-hydroxyphenyl)-9-{[2-(trifluoromethoxy)phenyl]acetyl}-1,3,9-triazaspiro[5.5]undecan-2-one + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 5-(4-fluoro-2-{[(3S)-oxolan-3-yl]oxy}phenyl)-9-{[2-(trifluoromethoxy)phenyl]acetyl}-1,3,9-triaza-spiro[5.5]undecan-2-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 5h;	52%

(2S,3R,4R,5S,6R)-2-(3-(4-hydroxybenzyl)-4-methylphenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (333360-66-0) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 1-methyl-2-[4-((S)-tetrahydrofuran-3-yloxy)-benzyl]-4-(β-D-glucopyranos-1-yl)-benzene (892486-47-4)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 60 - 80℃; for 22h;	46%

6-(3-azabicyclo[3.1.0]hexan-6-yl)-5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 5-methyl-1-(tetrahydro-2H-pyran-2-yl)-6-(3-((S)-tetrahydrofuran-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-indazole

Conditions	Yield
With potassium carbonate at 110℃; for 16h;	40%

(R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) + 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (269409-70-3) → 2-(4-((S)-tetrahydrofuran-3-yloxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1416157-64-6)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 85℃; for 15h;	30%

4-(4-methyl-2-((1s,4s)-4-methylcyclohexylamino)-6-(oxetan-3-yloxy)pyrimidin-5-yl)phenol + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 4-methyl-N-((1S,4S)-4-methylcyclohexyl)-6-(oxetan-3-yloxy)-5-(4-((S)-tetrahydrofuran-3-yloxy)phenyl)pyrimidin-2-amine

Conditions	Yield
With caesium carbonate; potassium iodide In N,N-dimethyl-formamide at 20 - 90℃; for 4.5h;	30%

(6aS,8S)-4-iodo-6a,7,8,9-tetrahydro-6H-pyrido[3,2-b]pyrrolo[1,2-d][1,4]oxazin-8-ol + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (6aS,8S)-4-iodo-8-(((S)-tetrahydrofuran-3-yl)oxy)-6a,7,8,9-tetrahydro-6H-pyrido[3,2-b]pyrrolo[1,2-d][1,4]oxazine

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; Inert atmosphere;	28.68%

4-carbethoxypiperidine (1126-09-6) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → ethyl 1-[(3S)-tetrahydrofuran-3-yl]piperidine-4-carboxylate

Conditions	Yield
With potassium carbonate In acetonitrile at 70℃; for 24h;	27%

(1R,4R)-5-(6-(6-(3-azabicyclo[3.1.0] hexan-6-yl)-5-methyl-1H-indazol-1-yl)-2-methylpyrimidin-4-yl)-2-oxa-5-azabicyclo[2.2.1]heptane + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (1R,4R)-5-(2-methyl-6-(5-methyl-6-(3-((S)-tetrahydrofuran-3-yl)-3-azabicyclo[3.1.0] hexan-6-yl)-1H-indazol-1-yl)pyrimidin-4-yl)-2-oxa-5-azabicyclo[2.2.1]heptane

Conditions	Yield
With potassium carbonate In acetonitrile at 110℃; for 24h; Inert atmosphere;	19%

Upstream product

• 86087-24-3 (R)-3-Hydroxytetrahydrofuran 
• 98-59-9 p-toluenesulfonyl chloride 

Downstream Products

• 864070-44-0 empagliflozin 
• 915095-99-7 (2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(4-chloro-3-(4-(((S)-tetrahydrofuran-3-yl)oxy)benzyl)phenyl)tetrahydro-2H-pyran-3,4,5-trityl triacetate 
• 915095-87-3 (S)-(2-chloro-5-iodophenyl)(4-((tetrahydrofuran-3-yl)oxy)phenyl)methanone 

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